Differential regulation of bradykinin receptor density, intracellular Ca2+, and prostanoid release in skin and foreskin fibroblasts. Effects of cell density and interleukin-1alpha.

1. Bradykinin (BK) receptors, cytosolic Ca2+, and prostanoids were studied in human skin and foreskin fibroblasts. 2. Bmax values of BK receptors were higher in foreskin than in skin fibroblasts, increasing with cell densities in both cell types. IL-1alpha-dependent receptor induction was blocked by cycloheximide. 3. BK-stimulated cytosolic Ca2+ elevation was higher in confluent than in non-confluent cultures and larger in foreskin than in skin fibroblasts. Responses were not enhanced after IL-1-alpha-induced up-regulation of BK receptors. 4. Intrinsic prostanoid production was higher in foreskin than in skin fibroblasts at comparable cell densities. In foreskin, but not in skin fibroblasts, BK stimulation increased the release of PGE2 10 fold and that of 6-oxo-PGF1alpha 6-7 fold. 5. Preincubation with IL-1alpha had a marked effect on prostanoid release in foreskin fibroblasts only. Subsequent BK stimulation increased the release of PGE2 and 6-oxo-PGF1alpha 7-10 fold in skin fibroblasts while this increase was only 30% in foreskin fibroblasts. Release of TXA2 reached values up to one third of the other prostanoids. The IL-1alpha induced rise in BK-stimulated PGE2 synthesis was fully abolished by specific inhibition of cyclo-oxygenase 2. 6. IL-1alpha sensitized BK-stimulated prostanoid synthesis and modulated prostanoid patterns differently in fibroblasts from skin and foreskin. The IL-1alpha effects on prostanoid release were not related to BK receptor numbers nor to the BK-stimulated Ca2+ signal but appear to be due to induction of prostanoid synthesizing enzymes. Foreskin fibroblasts seem to be unique and significantly different from fibroblasts of other skin locations in respect to their response to inflammation-associated kinins and cytokines.

[Management of children and adolescents with kidney transplantation]. / Betreuung von nierentransplantierten Kindern und Adoleszenten.

Successful renal transplantation is widely accepted as the treatment of choice for end-stage renal failure in infants, children and adolescents. The major issues currently requiring consideration when contemplating renal transplantation in the mentioned patients are: primary renal disease, psychosocial status, life-related versus cadaver donor allograft, optimal immunosuppressive regimen including cyclosporine, and maximization of growth and pubertal development. In transplanted adolescents, noncompliance is now a major problem, ranking only second to rejection as a cause of graft loss.

[Simple coagulation prophylaxis using low-molecular heparin enoxaparin in pediatric hemodialysis]. / Einfache Koagulationsprophylaxe mit dem niedermolekularen Heparin Enoxaparin in der pädiatrischen Hämodialyse.

The use of low molecular weight heparins for the prevention of clotting in extracorporeal circulation during hemodialysis has been reported in adults. In seven children (aged 7 to 18 years) with end stage renal failure an initial bolus of the low molecular weight heparin enoxaparin (dosage: 24 to 36 mg/m2) provided simple and proper anticoagulation with no hemorrhage during at least four hours. The tolerance was excellent.

[Physiological basis for the therapy of water, electrolyte and acid-base imbalance in infants and children]. / Physiologische Grundlagen zur Therapie der Wasser-, Elektrolyt- und Säure-Basen-Störungen im Säuglings- und Kindesalter

The therapeutic measures in the treatment of water, electrolyte and acid-base disturbances is based on the utilization of renal regulatory mechanisms. The treatment in infancy and childhood differs from that in adulthood mainly by the fact that kidney function of the small human being is quantitatively more limited due to its developmental status. Quantity and quality of kidney function in infancy and childhood are discussed. The capacity of the kidney to regulate the amount and composition of body fluids in this age group is less broad. In treating disturbances of water, electrolyte and acid-base metabolism it is, therefore, important to make use of simple diagnostic aids to assess individual renal function. A conceptual scheme for treatment is presented.

Acyclovir-induced renal failure: course and risk factors.

Of 19 children treated with high-dose intravenous acyclovir, 7, all of whom had encephalitis, also had a restricted fluid intake. Of these, 3 experienced non-oliguric renal insufficiency (plasma creatinine up to 176, 250 and 351 mumol/l, respectively) which resolved within 1 week of discontinuing acyclovir. Renal function was stable in the remaining 4 patients in this group and in the 12 children treated with acyclovir but without fluid restriction. We suggest the decreased renal function resulted from intratubular acyclovir crystalluria.

Cough and converting enzyme inhibitors.

Persisting cough developed in three children treated with converting enzyme inhibitors. The symptoms disappeared within 3-7 days after withdrawing medication. These observations in children complement previous reports in adults and indicate that cough may be induced by treatment with these agents.

Lipoprotein metabolism in nephrotic syndrome in childhood.

In nine patients with proteinuric nephrotic syndrome (NS), significant negative correlations were shown between plasma albumin and cholesterol (r=-0.85, p less than 0.005) and between plasma albumin and low density lipoprotein (LDL)-apoprotein B (ApoB) (r=-0.84, p less than 0.005), whereas there was no such correlation in ten matched ntrol patients. LDL-ApoB (182.8 +/141.2 MG/DL), cholesterol (249.3 +/-190.2 mg/dl) and triglycerides (40.8 +/- 23.5 mg/dl) were all elevated above controls. Control values: LDL-ApoB: 75.4 +/-25.0 mg/dl, -cholesterol: ll9.3 +/-27.6 mg/dl and -triglycerides: 29.2-17.9 mg/dl. The patients with proteinuric NS also exhibited a negative correlation between plasma triglyceride levels and plasma lipoprotein lipaseactiveiy (r=-0.79, p less than 0.02), which was not observed in controls. The hepatic triglycerice lipase (H-TGL) showed a mean activity of 22.2 +/- 10.7 mumol/ml FFA, which was not different form the control value of 21.2 +/-3.9 mumol/ml FFA. Not only LDL-cholesterol values were elevated in the patients with proteinuric NS, but high density lipoprotein (HDL)-cholesterol as well. HDL-cholesterol in proteinuric NS: 68.6 +/- 29.0 mg/dl, controls: 45.7 +/- 8.5 mg/dl. Twelve patients with NS in remission showed no correlation between plasma albumin and cholesterol and plasma albumin and LDL-ApoB respectively. The concentrations of LDL-ApoB (92.2 +/- 24.5 mg/dl),-cholesterol (121.7 +/- 37.1 mg/dl) and -triglycerides (28.9 +/-18.9 mg/dl) were within the normal range. No significan correlation was found between plasma triglyceride levels and plasma lipoprotein lipase activity (r=0.38, p greater than 0.2), and H-TGL activity, at 24.1 +/-9.3 mumol/ml FFA, was not different from control. In contrast to the complete normalization of LDL-cholesterol level, the HDL-cholesterol level remained slightly above control (HDL-cholesterol: 57.0 +/- 17.6 mg/dl). The hyperlipoproteinaemia in NS represents a combination of an increasents a combination of an increased hepatic lipoprotein synthesis and a decreased catabolism of triglyceride rich lipoproteins as indicated by an insufficiency of the lipoprotein lipase. The simultaneous elevation of LDL- and HDL-cholesterol suggests at most a moderate degree of atherogeneity of the hyperlipoproteinemia in NS.

[Management of hypercholesteremia by extracorporeal immune adsorption]. / Behandlung einer Hypercholesterinämie durch extrakorporale Immunadsorption.

Reduction of plasma cholesterol by extracorporeal immune elimination of low density lipoproteins (LDL) as an efficient approach to the treatment of familial hypercholesterolemia is described. LDL was removed from the plasma by immune adsorption on Sepharose-bound sheep antibodies against apo B, the protein fraction of LDL. To prevent the possibility of sensitization by the sheep antibodies, F(ab')2 fragments were used and the antibody containing Sepharose was underlaid by LDL containing Sepharose. Within a treatment time of 4 1/2-5 hours a reduction of the total plasma cholesterol by 70-80% was obtained. The mean reduction of the cholesterol concentration was more than 40% with a 14-day interval between two treatments. The concentration of other plasma proteins was not affected. The 11 treatments achieved so far were well tolerated and no side effects could be observed.

[Hemolytic-uremic syndrome in children: a 19-year retrospective study]. / Hämolytisch-urämisches Syndrom bei Kindern: Retrospektive über 19 Jahre.

Forty-two children (22 girls and 20 boys, ranging in age between 2 months and 13 years, median age 17 months) were admitted with acute hemolytic-uremic syndrome to the University Children's Hospital, Berne from 1973 to 1991. Seventeen patients developed hypertension and 30 renal failure. Three out of the 19 cases necessitating acute dialysis progressed to end stage renal failure. Four out of the 7 patients with signs of severe central nervous system involvement died. The initial clinical course was consistently more favourable in 35 patients with diarrheal prodrome. Increased protein excretion in association with high blood pressure was observed in 4 patients with initial favourable course who were examined one year after disease onset. This study indicates the generally favourable immediate prognosis of childhood hemolytic uremic syndrome and the possible persistence of high blood pressure and pathological proteinuria on follow-up.

Specific and non specific stimulation of prostaglandin release by human skin fibroblasts in culture.--Are changes of membrane fluidity involved?

In order to study a bidirectional relationship between changes of membrane fluidity and prostaglandin synthesis, the arachidonic acid cascade was stimulated in cultured human skin fibroblasts by unspecific stimuli (hypotonicity, low calcium concentrations) and by the specific stimulus, bradykinin. Fluorescence anisotropy of trimethylammoniumdiphenylhexatriene was used to measure membrane fluidity in cell monolayers. Hypotonicity or low calcium concentrations induce membrane fluidisation and prostaglandin synthesis. However, after specific stimulation of prostaglandins with bradykinin (at normocalcic and isotonic conditions) a rigidification of plasma membranes was observed in living cells. Fluidisation of membranes and bradykinin activate phospholipase A2 and induce prostaglandin synthesis. Although in cell membrane preparations increased phospholipase A2 activity leads to fluidisation, in our model a membrane fluidisation was not observed after stimulation of phospholipase with bradykinin. This suggests that in living cells a fluidizing effect of lysolecithin resulting from phospholipase A2 activation may be rapidly counteracted by its removal. A decrease of phosphatidylcholin content and consequently a rigidification of the membrane may ensue. Thus, the cell culture model using two different ways of stimulating phospholipase activity, helps to define the directional relationship between changes of membrane fluidity and activation of phospholipase and the arachidonic acid cascade in living human cells.

[An avoidable cause of parental anxiety and unnecessary medical workup: diaper crystals (pannolithiasis)]. / Eine vermeidbare Ursache von elterlicher Besorgnis und unnötigen medizinischen Abklärungen: Windelsteine (Pannolithiasis).

Five infants aged 6 to 23 months had a history of passing crystals in urine. They were not ill, but micturition was reported to be associated with pain in two of them. Physical examination was normal, and urinalysis and culture were negative. In one case we observed "jelly-like crystals" of about 2 mm diameter which dissolved spontaneously in tap water. When the parents were re-questioned it became evident that all used a new brand of highly absorbent diapers. "Jelly-like crystals" developed in our laboratory when the absorbent material of the new diapers was put in contact with urine or tap water. The new highly absorbent diapers help to keep the baby dry. However, "jelly-like crystals" may be observed and possibly alarm both parents and physicians. Information for parents and physicians may avoid unnecessary anxiety or medical workup.

[Levamisole in children with frequently recurring idiopathic nephrotic syndrome]. / Levamisol bei Kindern mit häufig rezidivierendem idiopathischem nephrotischem Syndrom.

10 children (8 boys and 2 girls) with frequently relapsing idiopathic nephrotic syndrome were treated with levamisole (5 mg/kg weekly). In 6 children with steroid dependent nephrotic syndrome a marked reduction in steroids by 62% to 75% was possible. Severe, transient neutropenia was observed in one patient. Levamisole failed to influence the disease course positively in 3 patients with relapses associated with intercurrent illness. It is concluded that levamisole may favourably influence steroid dependence in children with frequently relapsing idiopathic nephrotic syndrome.

Histological features of glomerular immaturity in infants and small children with normal or altered tubular function.

In children with renal tubular disorders the existence of retarded histological features of glomerular maturation has been suggested by our group. However, no valuable information is available on the frequency of histopathologically immature glomeruli in the normal kidney. For this reason we established a simple, semiquantitative definition of postnatal glomerular development: immature glomeruli (with at least half of the circumference of capillary loops densely lined with cuboidal epithelial cells), intermediate glomeruli (circumference of capillary loops lined with at least five adjoining cuboidal cells), and mature glomeruli. This definition was applied in a set of 71 normal kidneys from ages birth to 5 years. The relative frequency of the mentioned stages of glomerular maturation was strongly age dependent. In comparing the patients data with the normal findings it was possible to separate patients with the finding of disproportionately high fractions of immature glomeruli, provided the right age at biopsy is chosen. It is therefore concluded that the previous suspicion of late glomerular maturation may be validated in at least in some bioptic specimens.

[Simplified determination of proteinuria in children using a single urine sample]. / Vereinfachte Bestimmung der Proteinurie bei Kindern mittels einer einzigen Urinprobe.

In children and adolescents the evaluation of proteinuria is cumbersome because of the need to obtain timed urine collections. The protein/creatinine ratio (using a Coomassie blue binding technique and a kinetic Jaffe reaction, respectively) measured in 134 pediatric patients with renal disease aged 2 months to 16 years correlated closely with the overnight urine protein excretion rates using the statistical approach suggested by Bland and Altman to compare methods of measuring some quantity. The upper limit of urinary protein/creatinine ratio measured in 252 healthy children and adolescents aged 4 to 19 years was shown to be 19 mg/mmol. No age-related differences in urinary protein excretion were noted in healthy subjects. The random urine protein/creatinine ratio provides an accurate assessment of quantitative protein excretion and avoids errors and difficulties associated with timed urine collection.

Persisting renotubular sequelae after cisplatin in children and adolescents.

UNLABELLED: Information on persisting renal sequelae after cisplatin in children and adolescents is limited. Twelve patients aged 4-20 years had been treated with cisplatin and were healthy 4-43 months after stopping chemotherapy. Plasma creatinine, calcium, albumin and hydrogen ion concentration, plasma and urinary sodium, chloride, phosphate and urate, and urinary magnesium and potassium were comparable in patients and controls. However, mean calciuria, magnesemia and potassemia were significantly reduced and bicarbonatemia increased in the patients. Calciuria, magnesemia, potassemia and bicarbonatemia were normal in 3 patients only, calciuria was below -2 SD control in 9 patients, renal magnesium deficiency was demonstrated in 5 patients (all with hypocalciuria as well), and 4 patients presented with hypokalemic metabolic alkalosis (all with magnesium deficiency and hypocalciuria). CONCLUSIONS: (1) Renotubular dysfunctions persist very often after cisplatin; (2) hypocalciuria is more frequent than hypomagnesemia; (3) the most severe tubulopathy after cisplatin includes hypocalciuria, renal magnesium deficiency and hypokalemic metabolic alkalosis.